Cannabidiol supplementation - Uptake into muscle and adipose, implications for sports nutrition

Despite the popularity of Cannabidiol (CBD) as a dietary supplement with purpoted health benefits from pain and anxiety management or a sleep aid there is really limited data on its benefits for athletes. In fact a pubmed search limited to clinical trials shows only 6 studies of which only 3 are specifically focused on healthy subjects with relevant exercise models (Isenmann et al. 2021, Cochrane-Snyman et al. 2021, Sahinovic et al. 2022).

PERFORMANCE STUDIES

The Isenmann et al. study showed some benefits of feeding 60mg CBD (we are not given any details on the full composition of product) as a one off dose post exercise. The study showed some changes in markers of muscle damage and though no significant between groups (CBD vs. Placebo) benefits or on post exercise recovery are demonstrated. However, this result would not be unexpected as its a single bolus.

In the Cochrane-Snyman et al. study there was an attempt to look at elbow extensor muscle damage following eccentric exercise and then a 150mg CBD supplement (75mg twice post exercise). The issue here is the supplement contained the same amount of other cannabinoids as it did CBD, so is this really a CBD only study? The trial also used untrained subjects which is a consideration, especially if we are too extrapolate to the exercising population. The results however demonstrate no beneficial effects on markers of muscle damage.

Finally, in a pilot study by Sahinovic et al. it was again an acute intake study in trained (vo2max 57+/-4ml.kg-1) with 300mg of ‘Synthetic CBD’ or Placebo provided orally 1.5hrs before exercise (60min run and 70% VO2max into a incremental run to exhaustion). Its difficult to pull data from the exercise component of the study but it may be negative as VO2 at a fixed workload increased but there are some changes in VO2max so there maybe some collection issues here or even potentially an impact on blood flow (Stanley et al. 2015). However, its unlikely a significant effect given no change in blood pressure. The take home no performance benefit.

BEYOND ACUTE USE

The consideration here is that these studies are acute in nature (single or dual dose studies). In a recent research study providing an escalating dose of CBD isolate (>95% CBD) over 28days demonstrated a cumulative response in muscle and fat with increasing CBD intake (Child & Tallon, 2022). The rodent study looked at doses equivalent to 21mg/kg, 80.5mg/kg and 161mg/kg in humans and the accumulation in muscle liver and fat vs. a placebo group. Group effects (male + female) show increases across all tissues in dose dependent manner vs placebo.

The levels of fat in the liver are circa 5-7% (Petaja & Ski-Jarvinen, 2016), 5% in muscle (Maddocks et al. 2014) and 15-30% in adipose (Abernathy & Black, 1996). Putting aside age, diet, training status and analytical method (removal or not of visible intramuscular adipose)(Schrauwen-Hinderling et al. 2006) there seems to be a logical relationship between the level of fat (adipose + triglycerides) and first-pass metabolism by the liver and the retention of CBD in tissues.

This raises a number of issues in relation to proposed optimal supplementation as well as possible safety issues dependant on potential washout. If CBD is metabolised in a similar manner to THC then we may see continued excretion of CBD from the tissues in heavy CBD uses in the range of 80days (Ellis et al. 1985). However, levels of activity, fasting and stress may accelerate that process (Gunasekaran et al. 2009). As a safety issue we should consider what are appropriate recovery periods and markers in toxicity trials to take such concerns into account.

From the view of dosing and sports performance then as with the likes of creatine and beta-alanine a “CBD loading phase” followed by a “maintenance phase” or a longer low dose leading phase should be considered (we believe this article is the 1st time such issues have been considered). There may also be gender effects here given women typically have higher body fat levels, so are women what we could consider “Super responders” and at the other extreme athletes with very low body fat as “none or low responders”? At what point optimal levels to deliver a beneficial but safe physiological dose response are not known but clearly the cumulative effects in muscle and adipose may suggest that over time there maybe a “optimal” zone for performance and or recovery for those engaged in intense exercise.

SUMMARY

The data is simply not present for an acute or chronic effect of CBD for the enhancement of athletic performance and or recovery. Similarly, a major concern of study designs is they are often not fit for purpose. They are often designed for elite athletes despite being funded from consumer facing supplement companies. The average consumer is not elite and will in the vast majority of cases not have a VO2max over 65mls/kg so what are studies being designed in that manner. Often the answer is simple it would be easier to detect and effect in that population. But the results are exploited as if they equally apply to the average or every day gym worrier. What we need to see is relevant endpoints for the average consumer not activities to exhaustion lasting hours and hours or at a threshold of max that Joe bloggs cannot reach.

We already see a big push of the industry making promises that CBD is safe, its efficacious for gym goers but the facts is we simply don’t have the data to prove this. The data is coming but I see trials biased towards a positive effect rather than truly providing “proof before promises” approach that can inform the the “REAL” consumer. Here’s hoping the industry take an more ethical stance and really consider how they should design their safety and efficacy trials.

References

Isenmann E, Veit S, Starke L, Flenker U, Diel P. Effects of Cannabidiol Supplementation on Skeletal Muscle Regeneration after Intensive Resistance Training. Nutrients. 2021 Aug 30;13(9):3028.

Cochrane-Snyman KC, Cruz C, Morales J, Coles M. The Effects of Cannabidiol Oil on Noninvasive Measures of Muscle Damage in Men. Med Sci Sports Exerc. 2021 Jul 1;53(7):1460-1472.

Sahinovic A, Irwin C, Doohan PT, Kevin RC, Cox AJ, Lau NS, Desbrow B, Johnson NA, Sabag A, Hislop M, Haber PS, McGregor IS, McCartney D. Effects of Cannabidiol on Exercise Physiology and Bioenergetics: A Randomised Controlled Pilot Trial. Sports Med Open. 2022 Mar 2;8(1):27.

Stanley CP, Hind WH, Tufarelli C, O'Sullivan SE. Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation. Cardiovasc Res. 2015;107:568–578.

Child, R.B.; Tallon, M.J. Cannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue. Nutrients 2022, 14, 2101. https://lnkd.in/ePEemV7Z

Petäjä EM, Yki-Järvinen H. Definitions of Normal Liver Fat and the Association of Insulin Sensitivity with Acquired and Genetic NAFLD-A Systematic Review. Int J Mol Sci. 2016;17(5):633. Published 2016 Apr 27. doi:10.3390/ijms17050633

Abernathy RP, Black DR. Healthy body weights: an alternative perspective. Am J Clin Nutr. 1996 Mar;63(3 Suppl):448S-451S.

Maddocks M et al. Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD. European Respiratory Journal Nov 2014, 44 (5) 1188-1198

Schrauwen-Hinderling VB, Hesselink MK, Schrauwen P, Kooi ME. Intramyocellular lipid content in human skeletal muscle. Obesity (Silver Spring). 2006 Mar;14(3):357-6

Ellis GM, Jr, Mann MA, Judson BA, Schramm NT, Tashchian A. Excretion patterns of cannabinoid metabolites after last use in a group of chronic users. Clin Pharmacol Ther. 1985;38:572–578

Gunasekaran N, Long LE, Dawson BL, Hansen GH, Richardson DP, Li KM, Arnold JC, McGregor IS. Reintoxication: the release of fat-stored delta(9)-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure. Br J Pharmacol. 2009 Nov;158(5):1330-7